The present invention relates to a method for producing a fat mixture of xcex2-sitosterol, which mixture is health beneficial, homogeneous and stable, lowers the serum total cholesterol and LDL-cholesterol levels, and contains the xcex2-sitosterol in a partly dissolved and/or microcrystalline form.
A high serum total cholesterol level, hypertension and smoking are the main risk factors associated with a heart disease (1). There are several sterols of plant origin that are distinguished from cholesterol only by side chain substituents and by the degree of saturation. Most of the higher plants produce 24xcex1-substituted sterols (24-methyl- and 24-ethylsterols). Sitosterols are mixtures of xcex2-sitosterol (stigmasta-5-en-3xcex2-ole) and certain saturated sterols, such as xcex2-sitostanol, containing sterols not less than 95%, and unsaturated sterols not less than 85%. Sitosterols are broadly present in plants, such as in wheat and rye germ oils, corn oil, and commonly in seed oils. Sitosterols are antihypercholesterolemic agents that inhibit absorption of cholesterol in the intestine, and through the inner walls of blood vessels (2). Sitosterols play a role in the treatment of atherosclerosis when administered in doses of 2-3 grams., three times a day. In the western diet, the daily intake of xcex2-sitosterol, stigmasterol and campesterol from food is about 200-400 mg (3), which is of about the same order as our daily cholesterol intake from food.
At the beginning of 1950""s, it was recognized that as a result of the addition of xcex2-sitosterol to the feed of cholesterol fed chicken and rabbits, the cholesterol levels were lowered in both test animals, and moreover, this addition of xcex2-sitosterol prevented atherogenesis in rabbits (4). The use of sitosterol and soy bean sterols for lowering cholesterol levels was studied intensely in 1950""s and 1960""s (5), and indeed, preparations thereof lowered cholesterol levels by about 10% (6). It was then discovered that the activity of xcex2-sitosterol was based on the inhibition of absorption of cholesterol, and that sterols of plant origin were themselves poorly absorbed (7). The mechanism which inhibits the cholesterol absorption was considered to be based on crystallization and coprecipitation of cholesterol and xcex2-sitosterol. Mattson et al. (8) showed that 1 gram of xcex2-sitosterol reduces by 42% the absorption of cholesterol from food containing 500 mg of cholesterol. The reduction of plasma cholesterol may be due to the increased activity of LDL-receptors.
xcex2-Sitosterol is a lipophilic compound. In contact with the lipid membranes of intestinal walls, xcex2-sitosterol will not be absorbed due to its poor water solubility, or only a minor proportion of it will be absorbed; when administered orally, only less than 5% of it will be absorbed (9). The activity of xcex2-sitosterol is based on competitive inhibition of cholesterol absorption in the intestine (10). xcex2-sitosterol interferes with cholesterol resorption and reresorption in the small intestine (11). It is considered that this results from the similarity between the chemical structures of cholesterol and xcex2-sitosterol (12). Several studies carried out under various conditions have shown that phytosterols lower LDL-cholesterol levels. It is further recognized that serum phytosterols correlate with HDL-levels. xcex2-sitosterol reduces synthesis of cholesterol in the liver by affecting the gene expression of HMG-CoA reductase (13). Richter W et al. (14) have shown that xcex2-sitosterol lowers by 10-15% the total serum cholesterol level, and by 19% the LDL-cholesterol level, by inhibiting the absorption of cholesterol in the intestine. In a study, nine adult patients were administered for 5 days with 500 mg of cholesterol, as well as with 1 gram of xcex2-sitosterol, or 2 grams of xcex2-sitosteryl oleate. The absorption of cholesterol was decreased by 42% when administering xcex2-sitosterol, and by 33% when administering xcex2-sitoteryl oleate (15). Uchita et al. (16) have recognized that in female rats, sitosterol inhibits absorption of cholesterol, and lowers cholesterol balance in plasma and liver. Vahouny et al. (17) have discovered that sitosterol inhibits absorption of cholesterol in rats by 54%.
Finnish patent application No. 964951 discloses an agent for lowering the cholesterol level in serum, and the use thereof. This application relates to the use of an ester of xcex2-sitostanol with a fatty acid or a mixture of esters of xcex2-sitostanol with a fat acid as a fat component or as a fat substitute in food products, to the use thereof as such, complementing the diet, and to the compound itself.
Finnish patent publication No. 98 730 discloses a method for producing a substance to lower high serum cholesterol levels. In the method xcex2-sitostanol, obtained from xcex2-sitosterol by hydrogenating in an organic solvent in the presence of palladium on carbon as a catalyst, and a plant oil are used to produce an ester of xcex2-sitostanol with a fatty acid, or a mixture of such esters, employing the transesterification technique in the presence of a sodium ethylate catalyst.
Both of these patent publications mentioned above disclose a method for modifying xcex2-sitosterol to obtain a derivative thereof soluble in fats, wherein soluble xcex2-sitostanol fatty acid esters are produced therefrom, as well as the use of the compounds obtained as agents to lower serum cholesterol levels.
Naturally occurring xcex2-sitosterol is a crystalline compound. As is known, free sterols like xcex2-sitosterol are dissolved only scarcely in oil and fat, and therefore, derivatives of xcex2-sitosterol, for instance esters that are significantly more soluble in fats are produced for practical reasons, even though, according to some studies (15), these derivatives do not inhibit the absorption of cholesterol as effectively as the free xcex2-sitosterol. Such derivatives soluble in fats may be mixed much more easily into nutrition products to form a homogeneous mixture than a solid, insoluble, coarse xcex2-sitosterol powder. However, such processing to obtain a xcex2-sitosterol derivative entails additional costs for the product. Further, the hydrogenation of xcex2-sitosterol to xcex2-sitostanol is necessarily carried out using an organic solvent so that traces of it, as well as traces of the metal catalysts used, may be present in the esterified end product. In addition, the esterified product is no longer a naturally occurring substance but a man made artificial chemical compound.
An object of the invention is to provide a method for producing a fat mixture of xcex2-sitosterol, which is health beneficial, homogeneous and stable, lowers the total serum cholesterol and LDL-cholesterol levels, and contains the xcex2-sitosterol in a partly dissolved and/or in a microcrystalline form. Another object of the invention is to use such a homogeneous stable fat mixture of xcex2-sitosterol containing it in a partly dissolved and/or in a microcrystalline form in fat preparations or food products as an agent that lowers the cholesterol level in serum, as well as to use this mixture as such to complement the diet.
The main characteristic features of the method and use according to the present invention are disclosed in the appended claims.
We have discovered that xcex2-sitosterol may be made partly soluble and/or micro-crystalline with the following procedure. The problems and disadvantages associated with the state of the art may be avoided with the solution of the present invention. According to the method of the invention, xcex2-sitosterol and food grade oil are mixed, and this mixture is heated until all solids are dissolved in oil. After cooling, water is added into the mixture at the temperature thereof, thereby dispersing it. The result will be a homogeneous, stable, fat-like, almost white mass with a consistency closely resembling that of butter, or an oily mixture, depending on the amounts of the components. This homogeneous and stable paste is particularly suitable for being mixed into food products, for instance.
The starting material in this method is xcex2-sitosterol that may comprise 80-100% of xcex2-sitosterol and xcex2-sitostanol, and as impurities 0-20% of other sterols and stanols. This starting material containing xcex2-sitosterol, or xcex2-sitosterol may be mixed with the food grade oil in an amount of 0.5-80%, preferably 10-30%, the resulting pasty product having an appearance and a viscosity closely resembling those of butter, and being easy to handle. The higher the percentage of xcex2-sitosterol in the mixture, the harder the mass will be. On the other hand, if the amount of xcex2-sitosterol present in the mixture is less than 10% calculated from the amount of the oil, the viscosity of the mass will decrease, and the consistency thereof is clearly more like that of an oil. As a food grade oil, any cooking oil or any food grade oil or fat, or oil or an oily compound of animal origin, and suitable for human consumption may be used, for instance cod-liver oil, or any edible oily substance of plant or animal origin, or mixtures thereof. Preferred oils are rapeseed oil, turnip seed oil, sunflower oil, soy bean oil, corn oil, and olive oil. The amount of oil is 5-90%, preferably 60-85%, by weight of the mass of the mixture. Water used may be any food grade water, the percentage thereof being 5-30%, preferably 10-20%, by weight of the mass of the mixture.
In this method, a mixture of the starting material containing xcex2-sitosterol and oil is heated at the temperature of 80-140xc2x0 C., preferably at 100-120xc2x0 C., until the solid starting material containing xcex2-sitosterol is dissolved in oil. After cooling the mixture in a known manner to the temperature of 40-80xc2x0 C., preferably to 50-70xc2x0 C., water is added thereto essentially at the temperature of the mixture. Texture stabilizing surface active agents, such as polysorbate (Tween 80, Polysorbat 80), egg lecithin, or soy bean lecithin, known as emulsifying agents, may optionally be added to the mixture in an amount of 0.05-8.0%, by weight. If necessary, stabilizing agents, antioxidants, or other suitable food additives well known in the art, such as sodium chloride, mineral salt, preserving and flavouring agents, and/or various vitamins, for instance the vitamins A and E, food colours and phytophenols may be added. The mixture thus prepared is homogeneous and stable under conventional conditions for storing food products. In the mixture, xcex2-sitosterol is in a partly dissolved and/or microcrystalline form. If required, xcex2-sitosterol may also be dissolved in an oil as described above, and this xcex2-sitosterol/oil mixture may be used as such in food production.
The method of the invention makes it possible to produce, in a simple and economic way, a fat mixture of xcex2-sitosterol which is health beneficial, homogeneous and stable, reduces absorption of cholesterol in the intestine, thus lowering the serum total cholesterol and LDL-cholesterol levels, and contains the xcex2-sitosterol in a partly dissolved and/or microcrystalline form. This method uses a naturally occurring xcex2-sitosterol, and a food grade oil or fat, without any organic solvents or complicated process steps. Even high doses of the resulting homogeneous stable fat mixture containing a naturally occurring xcex2-sitosterol may be consumed safely in food products daily, and used in food production and cooking to replace fat partly or totally. xcex2-sitosterol cannot be detected from food products by senses. By means of the thus prepared food products, absorption of cholesterol in the intestine may be inhibited, and total serum cholesterol and LDL-cholesterol levels may be lowered significantly. In addition, since xcex2-sitosterol replacing fat is not substantially absorbed, the proportion of absorbed fat is reduced, and thus the energy intake lowered.
Fat mixture containing xcex2-sitosterol may be added into food products that comprise fats of animal or plant origin, or mixtures thereof. Suitable food products are various processed meat products such as sausages and cold cuts, processed fish products, food products containing natural fatty acids, dairy products such as cheese, and several other food products containing edible fats or mixtures thereof, for instance sauces and dressings, mayonnaise, spices and spice mixtures, cereal, noodle and pasta products, ice cream, candies, chocolate, cakes, pastries, and the like, as well as edible fats for cooking and baking, and mixtures thereof.
The invention will now be illustrated with some preferred embodiments thereof described in the following examples, however, without intending to limit the invention solely thereto.